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Jaundice is the yellow discoloration of the skin, mucous membranes, and sclerae caused by elevated serum levels of bilirubin, a by-product of heme breakdown. Bilirubin is a lipophilic pigment and must bind to plasma albumin to be transported to the liver. It is then taken up by hepatocytes for conjugation with solubilizing sugars to form bilirubin diglucuronides (and, less commonly, monoglucuronides), which can be excreted into bile. Several factors can cause jaundice. While many of these processes are pathologic, physiologic jaundice in neonates, a benign process, accounts for the vast majority of clinically encountered jaundice in pediatrics.

Cause and Frequency

Jaundice may be secondary to an unconjugated or conjugated hyperbilirubinemia (Table 15-1). In general, unconjugated hyperbilirubinemia results from overproduction of bilirubin, impaired uptake of bilirubin by hepatocytes, or impaired conjugation. A primary cause of overproduction is hemolysis, which is usually associated with other laboratory abnormalities including anemia, elevated LDH, low haptoglobin, and increased reticulocyte count. Reduced uptake of bilirubin can be due to poor blood flow to the liver, certain drugs, and various inherited diseases. Impaired bilirubin conjugation is usually due to various inherited disorders, such as Gilbert syndrome or Crigler-Najjar, where the enzymes needed for conjugation are deficient.

Table 15-1. Common Causes of Jaundice in Infants and Children.

Conjugated hyperbilirubinemia occurs secondary to cholestatic conditions or direct hepatocellular injury. Cholestasis results from intra- or extrahepatic impairments in bile flow, and is accompanied by elevations in alkaline phosphatase and/or gamma-glutamyl transpeptidase (GGT). The differential diagnosis of cholestatic jaundice in the older child differs from diseases that present early in life. Young infants are more likely to have congenital anatomic anomalies, such as biliary atresia, or inborn metabolic disorders such as galactosemia. In contrast, older children are more likely to experience acquired or secondary liver diseases, such as cholelithiasis or sclerosing cholangitis. There is often an overlap between syndromes causing cholestasis and those resulting in hepatocellular injury. Generally, hepatocellular injury is accompanied by elevations in the ...

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